A gene involved in energy balance was associated with obesity among patients with psychiatric disorders, researchers found.

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A gene involved in energy balance was associated with obesity among patients with psychiatric disorders.

Note that the strongest, and most clinically relevant, association between the G allele of the CREB-regulated transcription coactivator (CRTC1) gene and weight gain was observed in women younger than 45 years.

A gene involved in energy balance was associated with obesity among patients with psychiatric disorders, researchers found.

In analyses of retrospective and prospective data, one particular allele of the CREB-regulated transcription coactivator (CRTC1) gene was protective against weight gain in psychiatric patients (P=0.003), Chin Eap, PhD, of Hopital de Cery in Lausanne, Switzerland, and colleagues reported online in JAMA Psychiatry.

"Our results suggests that CRTC1 plays an important role in the high prevalence of overweight and obesity observed in psychiatric patients," they wrote, adding that the gene also seems to play a role in obesity in the general population.

The CRTC1 gene -- mainly expressed in the brain where it may modulate leptin's anorexic effects -- has been shown to be involved in energy balance and obesity in animal models, but its role in human obesity isn't clear.

To assess its effects in psychiatric patients, the researchers looked at retrospective and prospective data, as well as population-based samples from Lausanne and Geneva university hospitals and private clinic data from Lausanne. Specifically, they focused on an initial sample of 152 psychiatric patients, and then attempted to replicate their findings in two independent psychiatric samples, one with 174 patients and another with 118 patients.

Eap and colleagues also looked at the gene's effects in two population-based samples, one with 5,338 people and another with 123,865 people.

Overall, they found in the main psychiatric sample that the polymorphism rs3746266A>G in the CRTC1 gene was associated with body mass index (BMI, P=0.003).

In all three psychiatric samples, carriers of this allele had a lower BMI than noncarriers (P=0.001, P=0.05, and P=0.0003, respectively, in each sample).

"The CRTC1 nonsynonymous polymorphism rs3746266A>G was associated with BMI in three independent psychiatric samples in which lower BMI values were measured in carriers of the G allele compared with noncarriers," the researchers wrote.

In a combined analysis that excluded patients who were taking drugs that induced weight gain, G-allele carriers had a 1.81-kg/m2 lower BMI than noncarriers, they reported (P<0.0001).

The strongest association was seen in women younger than 45, with a 3.87 kg/m2 lower BMI in G-allele carriers (P<0.0001), Eap and colleagues wrote.

In the population-based samples, a similar polymorphism -- the T allele of rs6510997C>T -- was associated with lower BMI (P=0.01) and lower fat mass (P=0.03).

The strongest association was seen in premenopausal women (P=0.02), they reported, adding that women taking oral contraceptives were also protected against fat accumulation, suggesting that estrogen levels "may modulate the effect of the CRTC1 polymorphism on fat accumulation."

The stronger associations among women could also be caused by a differential role of the leptin-mediating satiety pathway in the enhancement of CRTC1 activity, they wrote.

Either way, they noted, the effect size of this association "is clinically relevant and in a consistent direction with the one observed in psychiatric disorders."

The study was limited because most patients were not drug-naive and many had already developed weight gain due to previous treatments, so it wasn't possible to determine causality. It was also limited by the use of some self-reported data and by a potential lack of generalizability.

Still, the the researchers said the findings suggest that better identification of psychiatric patients at high risk of weight gain could "contribute to a better individualization of the pharmacological treatment in psychiatry." In addition, "CRTC1 could play a role in the genetics of obesity in the general population, thereby increasing our understanding of the multiple mechanisms influencing obesity."

The study was funded in part by the Swiss National Research Foundation, the National Center of Competence in Research, and the Swiss National Science Foundation.

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